Botox Group Research Articles

Radiological and clinical findings following distraction osteogenesis of the lower limb in children with or without botox injection: A preliminary report

Context: Limb lengthening correction according to Ilizarov distraction osteogenesis (DO) usually yields excellent results. While pediatric orthopedic surgeons anecdotally report that botulinum toxin A (Botox) alleviates spasm and pain during DO, no study has examined the effects of this surgery and Botox injection on muscle morphology in children. Aims: (1) To evaluate the clinical and radiological effects of lower limb lengthening in children and (2) the effects of adjunctive Botox muscle injection. Setting and Design: This was a center and randomized control trial. Methods: Seven children underwent tibial (n = 3) or femoral lengthening (n = 4) and were randomized to receive either a Botox or sterile saline solution. Quality of life and functional mobility outcomes, muscle testing, and magnetic resonance imaging examination were obtained at baseline, 12-, and 24-month postoperative. Muscle measurements were acquired on axial T1-weighted images and included: (1) total cross-sectional area (TCSA), (2) functional cross-sectional area (FCSA, fat-free area), (3) ratio of FCSA to TCSA, and (4) asymmetry between sides. Results: Physical performance improved at 12- and 24-month postoperative. Muscle strength remained functional across the three time points. A decrease in TCSA and FCSA was observed at 12-month follow-up in the operated thigh of patients undergoing femur lengthening, but muscle mass was regained at 24 months. However, TCSA and FCSA remained lower in the operated femur at 24 months. Similar findings were also observed in patients who underwent tibial lengthening. Patients in the Botox group appeared to have a slightly greater decrease in muscle mass and increase in fatty infiltration in the operated leg. Conclusions: Children undergoing DO preserved their muscle strength and improved physical performance 2-year postoperative. Our results suggest that muscle size and muscle mass remained lower in the operated leg; a finding that was slightly more prominent in children who received a Botox injection.

Intravesical injection of botulinum toxin A for treatment of interstitial cystitis/bladder pain syndrome: 13 years of experience

Objective To evaluate the efficacy of the intravesical injection of botulinum toxin A (BTX-A) and bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Methods We retrospectively reviewed 153 women with IC/BPS from January 2003 to December 2015. Of the 153 patients, 77 were treated with BTX-A(group A), the average age was (56.0±4.1) years old. 76 underwent bladder hydrodistention plus sodium hyaluronate (Cystistat) instillation (group B), the average age was (58.0±3.3) years old. The patients were evaluated using the O’Leary-Saint score, visual analog scale pain score, urinary frequency record and quality of life questionnaire before treatment and 1 week, 1, 3, 6 and 12 months after treatment. Results In group A, only 2 had acute urinary retention, 27 received a repeat injection, and 28 were lost to follow-up. In group B, 3 had urinary tract infection, 15 switched to BTX-A injection at 6 months because the treatment of hydrodistention plus Cystistat instillation is not good. 31 were lost to follow-up. BTX-A was shown to remain effective for up to 6 months after treatment. After repeated Chinese BTX-A injections, symptoms improved significantly. Hydrodistention plus Cystistat remained effective for up to 3 months after treatment. Conclusions Intravesical injection of BTX-A is a effective therapeutic option for patients with IC/BPS. The average duration of the effect of one dose of Chinese BTX-A was 6 months. Repeated injection of BTX-A is effective. Key words: Interstitial cystitis/bladder pain syndrome; Botulinum toxin-A; Intravesical injection; Hydrodistention; Sodium hyaluronate

Combined Effect Of Botulinum Toxin And Splinting On Motor Components And Function Of People With Stroke

Background and objective: Spasticity is one of the problems following stroke. Due to this increase in muscle tone, patients are confronted to problems in motor control and difficulties in activities of daily living and complications such as shortness and contracture. The aim of this study was to examine the effects of Simultaneous use of both splint and botulinum toxin-A (BTX-A) injection on spasticity, range of motion and upper extremity function in a 3-month period.Methods: The design of this study was a comparison between 3 groups of interventions, conducted in rehabilitation clinics in Tehran. Sixty people with chronic stroke were recruited. Based on the inclusion criteria, a total of 39 stroke patients after completing the consent forms were entered to intervention groups; splint or botulinum toxin injection or combined splint/botulinum toxin injection. They were followed up about 3 months and the evaluations were done monthly. Goniometry was the method to measure range of motion, and Modified Ashworth scale was used to examine the spasticity and the upper extremity function was scored based on Fugl-Meyer assessment. Statistical analysis was done using SPSS 17. And ANOVAs was used for comparison between groups and times. Significance was set at 0.05.Results: All outcome measures improved within each group but the differences between splint group and BTX-A group and the BTX-A-splint group was not significant in most outcomes during 3 periods (first evaluation until end of the first month, the end of first month until the end of second month, the end of second month until the end of the third month) (p> 0 / 05). The results also showed that the changes in elbow`s spasticity {p= 0.05} and wrist`s spasticity {p= 0.007} and upper extremity function { p = 0.04} were obvious between the three groups over the 3-months and the difference in the group of combined use of botulinum toxin and splint was more than other groups.Conclusion: In this study, the effects of botulinum toxin injection and Volar-Dorsal Wrist/Hand Immobilization splint and the combined use of botulinum injection and splint were obvious in all groups but was not significantly different between the interventions in a 3-month follow-up.

Effects of Botulinum Toxin A on Histology and Ultrastructure of Submandibular Salivary Gland in Rats

Introduction: Botulinum toxin A (BoNTA) has been used for treating hyperfunction of various glands such as sweat, lacrimal, and salivary glands. However, the long-term histological sequences are largely unknown. Objectives: The present study is to evaluate the histological and ultrastructural effects of BoNTA on submandibular salivary gland (SSG). Methods: Eighteen 6-week-old male albino rats received 0.1 ml of either saline (sham group, n=9) or BoNTA (BoNTA group, n=9) injection in the right SSGs. Of 9 rats in each group, 3 were terminated at 2, 4 and 12 weeks after the injection. The harvested SSGs were embedded and sectioned at 6µm, and stained with H&E for histological study. Ultrathin sections (60-90nm) were cut from1 mm3 pieces harvested from the center of SSGs, and mounted on copper grids for ultrastructural study using transmission electron microscope (TEM). Results: All sham SSGs showed normal acinar cells with rounded nuclei and regular striated ducts (SD) with characteristic basal striations. By TEM, acinar cells exhibited rounded nuclei, mitochondria, and secretory granules at cytoplasm. Numerous mitochondria presented in SD. Compared with these features, 2-week BoNTA-injected SSGs showed loss of spherical fashion and basal striations in serous acini and SD respectively, and the cell boundaries were not clear. TEM further revealed irregular nuclei of acinar cells and SD, and swollen mitochondria. In 4-week SSGs, some acini and ducts lost their spherical fashion and in some areas, these structures disappeared. Ruptured mitochondria were observed in acini and SD by TEM. However, all 12-week BoNTA-injected SSGs seemed to have similar structures to those of sham SSGs. By using scoring system for semi-quantifying the histological structural changes of BoNTA-injected SSGs, 2- and 4-week BoNTA-injected SSGs showed significantly higher scores as compared with their sham counterparts. However, no significant score difference was found between 12-week BoNTA-injected and sham SSGs. Conclusions: Although application of BoNTA results in significant changes in histological structures and ultrastructures of SSGs, these detrimental effects seems to be transient, and the major recovery occurs in 3 months. Thus, BoNTA can be used for treating SSG hyperfunction.

Safety and efficacy of letibotulinumtoxinA(BOTULAX®) in treatment of post stroke upper limb spasticity: a randomized, double blind, multi-center, phase III clinical trial

Objective: To investigate a new botulinum neurotoxin type A, termed letibotulinumtoxinA(Botulax®) and compare its efficacy and safety for post-stroke upper limb spasticity with that of onabotulinumtoxinA(Botox®). Design: A prospective, double-blinded, multicenter, randomized controlled clinical study. Setting: Six university hospitals in Korea. Subjects: A total of 187 stroke participants with upper limb spasticity. Interventions: Two kinds of botulinum neurotoxin type A were used. One set of injection was performed and total injected doses were 309.21±62.48U(Botulax) and 312.64±49.99U(Botox)(P>0.05). Main measures: Primary outcome was measured using the modified Ashworth scale for wrist flexors at week 4 and secondary outcome was measured using modified Ashworth scale for wrist flexors, elbow flexors, finger flexors, and thumb flexors as well as Global Assessment in spasticity, Disability Assessment Scale, and Caregiver Burden Scale. Safety measures including adverse events, vital signs and physical examination, and laboratory tests were also monitored. Results: The mean ages for the Botulax group were 56.81±9.49 and which for the Botox group were 56.93±11.93(P>0.05). In primary outcome, the change in modified Ashworth scale for wrist flexors was -1.45±0.61 in the Botulax group and -1.40±0.57 in the Botox group, and the difference between the two groups was -0.06(95% CI:-0.23–0.12,P>0.05). In secondary outcome, both groups demonstrated significant improvements with respect to modified Ashworth scale, Global Assessment in spasticity, Disability Assessment Scale, and Caregiver Burden Scale (P<0.05), and no significant difference was observed between the two groups (P>0.05). In addition, safety measures showed no significant differences between the two groups (P>0.05). Conclusions: The efficacy and safety of Botulax were comparable with those of Botox in treatment of post-stoke upper limb spasticity.

The Effect of Botulinum Toxin A on Ischemia-Reperfusion Injury in a Rat Model.

Introduction While studies using various materials to overcome ischemia-reperfusion (IR) injury are becoming increasingly common, studies on the effects of botulinum toxin A (BoTA) on IR injury in musculocutaneous flaps are still limited. The purpose of this study was to examine our hypotheses that BoTA provide protection of musculocutaneous flap from ischemia-reperfusion injury. Method Five days after pretreatment injection (BoTA versus normal saline), a right superior musculocutaneous flap (6 × 1.5 cm in size) was made. Ischemia was created by a tourniquet strictly wrapping the pedicle containing skin and muscle for 8 h. After ischemia, the tourniquet was cut, and the musculocutaneous flap was reperfused. Results The overall survival percentage of flap after 8 h of pedicle clamping followed by reperfusion was 87.32 ± 3.67% in the control group versus 95.64 ± 3.25% in the BoTA group (p < 0.001). The BoTA group had higher expression of CD34, HIF-1α, VEGF, and NF-kB comparing to control group in qRT-PCR analysis. Conclusions In this study, we found that local BoTA preconditioning yielded significant protection against IR injury in a rat musculocutaneous flap model.

Restriction of Postoperative Joint Loading in a Murine Model of Anterior Cruciate Ligament Reconstruction: Botulinum Toxin Paralysis and External Fixation.

Control of knee motion in small animal models is necessary to study the effect of mechanical load on the healing process. This can be especially challenging in mice, which are being increasingly used for various orthopedic reconstruction models. We explored the feasibility of botulinum toxin (Botox; Allergan, Dublin, Ireland) paralysis and a newly designed external fixator to restrict motion of the knee in mice undergoing anterior cruciate ligament (ACL) reconstruction. Nineteen C57BL/6 mice were allocated to two groups: (1) Botox group (n = 9) and (2) external fixator group (n = 10). Mice in Botox group received two different doses of Botox: 0.25 unit (n = 3) and 0.5 unit (n = 6). Injection was performed 72 hours prior to ACL reconstruction into the quadriceps, hamstring, and calf muscles of the right hind leg. Mice in external fixator group received an external fixator following ACL reconstruction. Mice were monitored for survival, tolerance, and achievement of complete knee immobilization. All mice were meant for sacrifice on day 14 postoperatively. No perceptible change in gait was observed with 0.25 unit of Botox. All mice that received 0.5 unit of Botox had complete hind limb paralysis documented by footprint analysis 2 days after injection but failed to tolerate anesthesia and were euthanized 24 hours after operation due to their critical condition. In contrast, the external fixator was well tolerated and effectively immobilized the limb. There was a single occurrence of intraoperative technical error in the external fixator group that led to euthanasia. No mechanical failure or complication was observed. Botox paralysis was not a viable option for postoperative restriction of motion and joint loading in mice. However, external fixation was an effective method for complete knee immobilization and can be used in murine models requiring postoperative control of knee loading. This study introduces a robust research tool to allow control of postoperative joint loading in animal models such as ACL reconstruction, permitting study of the effects of mechanical load on the biologic aspects of tendon-to-bone healing.

Repetitive transcranial magnetic stimulation versus botulinum toxin injection in chronic migraine prophylaxis: a pilot randomized trial.

BackgroundChronic migraine is a prevalent disabling disease, with major health-related burden and poor quality of life. Long-term use of preventive medications carries risk of side effects.ObjectivesThe aim of this study was to compare repetitive transcranial magnetic stimulation (rTMS) to botulinum toxin-A (BTX-A) injection as preventive therapies for chronic migraine.MethodsA pilot, randomized study was conducted on a small-scale sample of 29 Egyptian patients with chronic migraine, recruited from Kasr Al-Aini teaching hospital outpatient clinic and diagnosed according to ICHD-III (beta version). Patients were randomly assigned into two groups; 15 patients received BTX-A injection following the Phase III Research Evaluating Migraine Prophylaxis Therapy injection paradigm and 14 patients were subjected to 12 rTMS sessions delivered at high frequency (10 Hz) over the left motor cortex (MC, M1). All the patients were requested to have their 1-month headache calendar, and they were subjected to a baseline 25-item (beta version) Henry Ford Hospital Headache Disability Inventory (HDI), Headache Impact Test (HIT-6), and visual analogue scale assessment of headache intensity. The primary efficacy measures were headache frequency and severity; secondary measures were 25-item HDI, HIT-6, and number of acute medications. Follow-up visits were scheduled at weeks 4, 6, 8, 10, and 12 after baseline visit.ResultsA reduction in all outcome measures was achieved in both the groups. However, this improvement was more sustained in the BTX-A group, and both the therapies were well tolerated.ConclusionBTX-A injection and rTMS have favorable efficacy and safety profiles in chronic migraineurs. rTMS is of comparable efficacy to BTX-A injection in chronic migraine therapy, but with less sustained effect.

Cost-Effectiveness Analysis of Anticholinergics Versus Botox for Urgency Urinary Incontinence: Results From the Anticholinergic Versus Botox Comparison Randomized Trial.

This study aimed to compare the cost-effectiveness of Botox and anticholinergic (AC) medications for the management of urgency urinary incontinence (UUI). Cost and effectiveness data were analyzed from participants in the Anticholinergic versus Botox Comparison randomized trial of daily AC medication versus 100 U of intradetrusor Botox injection. Societal costs included the following: treatment costs, patient costs, and medical and nonmedical utilization during the 6-month trial. Quality-adjusted life-years (QALYs) were calculated based on questionnaire-derived utility measures and annualized based on data collected at baseline through 6 months. We also estimated the average direct costs for each treatment through 9 months - the duration of time when approximately half the Botox participants maintained adequate symptom control. Data were analyzed on the 231 women who completed a 6-month follow-up in the Anticholinergic versus Botox Comparison trial (119 AC and 112 Botox). The mean reduction in UUI episodes per day was not significantly different per group. The cumulative mean direct costs through the first 6 months also were similar: $1339 for the AC group and $1266 for the Botox group with AC costs exceeding Botox costs after 5 months. Both groups had considerable QALY gains. Annualizing the 6-month trial results to a 12-month measure, the AC and Botox groups averaged 0.702 and 0.707 QALYs, respectively. Estimates through 9 months favored Botox, showing that AC participants incurred a higher cost per month of adequate symptoms control ($305) compared with Botox participants ($207). Botox and AC medications have similar costs and effectiveness in the first 6 months of UUI treatment. If costs and outcomes are considered through 9 months, Botox may have significantly lower costs but similar UUI symptom control as AC.

Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis.

Botulinum toxin A (BTX-A) is a medical product that is used widely in cosmetics, and concern over the safety profile has increased among injectors and patients. The purpose was to enhance the statistical effect size using a meta-analysis to detect the incidence rate of adverse events (AEs) in the treatment of facial wrinkles. A systematic search was performed for randomized, double-blind, placebo-controlled trials published through July 2015. We searched 16 trials, including 42,405 individual participants, and found that in all enrolled facial rejuvenation studies, patients in the BTX-A group had significantly more AEs than those patients in the placebo group (RR=1.24; 95% CI 1.07-1.43; p=0.003). For crow's feet lines injection analysis, the BTX-A group did not exhibit any significant increase in AEs compared with the control group (RR=1.19; 95% CI 0.96-1.48; p=0.12), except in injection site hematoma (RR=2.14; 95% CI 1.13-4.07; p=0.02) in the treatment group. For frown wrinkle injection analysis, AEs were significantly observed in the BTX-A group (RR=1.47; 95% CI 1.23-1.77; p<0.0001), particularly headaches (RR=1.53; 95% CI 1.15-2.03; p=0.003), eyelid ptosis (RR=5.56; 95% CI 1.68-18.38; p=0.005), and heavy eyelids (RR=6.94; 95% CI 1.27-37.93; p=0.03). This meta-analysis confirmed the safety profile of BTX-A for glabellar and crow's feet lines, and BTX-A usage for the removal of upper facial wrinkles, which have some significant mild-to-moderate adverse profiles, including headache, eye disorder, eyelid ptosis, and heavy eyelids. Facial injectors should abide by the technical standards of neurotoxic drugs and be familiar with the local pharmacological effects to lessen the severe side effects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors www.springer.com/00266 .

The Protective Effects of Botulinum Toxin A Against Flap Necrosis After Perforator Twisting and Its Underlying Molecular Mechanism in a Rat Model.

The purpose of this study was to examine our hypotheses that botulinum toxin A (BoTA) protect necrosis of perforator flap from perforator twisting. Twenty-four rats were randomly divided into 2 groups. Twelve International Units of BoTA versus 1.2 mL normal saline was injected subdermally 3 days before flap elevation. In each group, bilateral before deep inferior epigastric perforator (DIEP) flaps, 5 × 3 cm in size, were created. The right and left (180 and 360 degrees of perforator twisting) DIEP flaps were separated. At 1 and 3 days postoperatively, skin above the perforator of the DIEP flaps was harvested to examine the degrees of gene expressions. Final survival percentage of flap and histology were assessed at postoperative day 5. The survival percentage of flap was significantly higher in the BoTA group than in the control group at both DIEP flaps after 180 and 360 degrees of perforator twisting at postoperative day 5 (95.23 ± 2.85% vs 91.00 ± 3.77%; P = 0.021 and 91.59 ± 2.87% vs 30.03 ± 6.91%; P < 0.001, respectively).Higher fibroblast density, enhanced epithelial necrosis, and inflammation were noted in the control group than in the BoTA group. In 180 degrees of perforator twisting group, BoTA may augment angiogenesis possibly via nuclear factor-κB-induced destabilization and the nuclear factor-κB/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway, whereas in the 360 degrees of perforator twisting group, the mechanistic target of rapamycin/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway may participate in BoTA-induced effective angiogenesis. We demonstrated that pretreatment with BoTA protects perforator flap caused by perforator at the pathological and molecular level using an experimental rat model.

Presurgical Botulinum Toxin A Treatment Increases Angiogenesis by Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor and Subsequent Superiorly Based Transverse Rectus Abdominis Myocutaneous Flap Survival in a Rat Model.

To date, there have been several experimental studies to assess tissue viability of transverse rectus abdominis myocutaneous (TRAM) flaps. Botulinum toxin A (BoTA) has gained popularity in many clinical fields, for a variety of therapeutic and aesthetic purposes. In addition, there have been reports regarding the positive effect of BoTA on flap survival by various mechanisms. In this study, we hypothesized that pretreatment with BoTA could augment the survival of TRAM flaps via increased hypoxia-inducible factor (HIF)1α/vascular endothelial growth factor (VEGF)-dependent angiogenesis.Twenty-four Sprague-Dawley rats were randomly divided into 2 groups: a control group and a BoTA group. Five days before superiorly based TRAM flap elevation, the BoTA group was pretreated with BoTA, whereas the control group was pretreated with normal saline. Gross flap survival rates were assessed, and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting were performed for the evaluation of angiogenesis-related factors (CD34, HIF-1α, and VEGF).In the BoTA group, the gross flap survival rate was significantly higher than that in the control group on both ipsilateral (92.78.3 ± 5.05% vs 86.8 ± 3.88%, P = 0.009) and contralateral (91.57 ± 5.79% vs 74.28 ± 11.83%, P < 0.001) sides.The relative mRNA expression of CD34 and VEGF was significantly higher in the BoTA group than that in the control group in every zone, whereas the relative mRNA expression of HIF-1α was significantly higher in the BoTA group than that in the control group on contralateral sides. The relative protein expression of CD34, VEGF, and HIF-1α was significantly higher in the BoTA group than that in the control group in every zone.In conclusion, we demonstrate that presurgical BoTA treatment might increase angiogenesis by HIF-1α/VEGF, subsequently increase superiorly based TRAM flap survival in a rat model.

Occlusal force characteristics of masseteric muscles after intramuscular injection of botulinum toxin A(BTX – A)for treatment of temporomandibular disorder

Our aim was to evaluate the occlusal force and therapeutic efficacy of the masseteric muscles after intramuscular injection of botulinum toxin A (BTX-A) for the treatment of patients with concurrent temporomandibular disorders (TMD) and bruxism. Thirty patients with TMD associated with bruxism were randomised into three groups (n=10 in each group), and treated by bilateral intramuscular injection of BTX-A into the masseter, placebo, or control. We used an occlusal force analysis system to collect several measures of occlusal force such as duration of biting and closing, the maximum occlusal force, and the distribution of occlusal force. The occlusal force in the intercuspid position was reduced in all three groups. There was a significant difference between the BTX-A and placebo groups (F(df=1)=8.08, p=0.01) but not between the control group and the other two(F(df=1)=4.34, p=0.047). The duration of occlusion was significantly increased in the BTX-A group after 3 months’ treatment (t=4.07, p=0.003). The asymmetrical distribution of occlusal force was reduced in all three groups, but not significantly so (Levene's test F(df=2)=0.25, p=0.78,ANOVA F(df=2)=0.50, p=0.61). Treatment of TMD with BTX-A is effective in reducing the occlusal force, but psychological intervention plays an important part in treatment.

Soluble N-ethylmaleimide-sensitive Factor Attachment Receptor (SNARE) Protein Involved in the Remission of Depression by Acupuncture in Rats

This study aims to investigate the molecular mechanisms of acupuncture in the remission of depression. A depressive disorder model was induced by exposing Sprague–Dawley rats to chronic unpredictable stress. The rats were divided into five groups: healthy (blank group) and stressed rats (model group), and stressed rats treated with acupuncture (acupuncture group), riluzole (riluzole group), acupuncture combined with botulinum toxin A (BTX-A) injection (acupuncture+BTX-A group) or riluzole combined with BTX-A injection (riluzole+BTX-A group). Behavioral analysis showed significant differences in sucrose consumption, weight, and horizontal or vertical movements between the model and both the riluzole and acupuncture groups. No obvious differences between the riluzole+BTX-A and acupuncture+BTX-A groups were found. Moreover, no significance differences in glutamate content in the hippocampus were found among the riluzole+BTX-A, acupuncture+BTX-A and model groups (p>0.05). Western blots and reverse transcription polymerase chain reactions were employed to detect protein and mRNA expressions of VGLUT2, SNAP25, VAMP1, VAMP2, VAMP7, and syntaxin1; no obvious differences among the riluzole+BTX-A, acupuncture+BTX-A and model groups were found. These data suggest that soluble N-ethylmaleimide-sensitive factor attachment receptor proteins are involved in the remission of depression in rats treated with acupuncture.

Intraoperative Endoscopic Botox Injection During Total Esophagectomy Prevents the Need for Pyloromyotomy or Dilatation.

Esophagectomy may lead to impairment in gastric emptying unless pyloric drainage is performed. Pyloric drainage may be technically challenging during minimally invasive esophagectomy and can add morbidity. We sought to determine the effectiveness of intraoperative endoscopic injection of botulinum toxin into the pylorus during robotic-assisted esophagectomy as an alternative to surgical pyloric drainage. We performed a retrospective analysis of patients with adenocarcinoma and squamous cell carcinoma of the distal esophagus or gastroesophageal junction who underwent robotic-assisted transhiatal esophagectomy (RATE) without any surgical pyloric drainage. Patients with and without intraoperative endoscopic injection of 200 units of botulinum toxin in 10 cc of saline (BOTOX group) were compared to those that did not receive any pyloric drainage (noBOTOX group). Main outcome measure was the incidence of postoperative pyloric stenosis; secondary outcomes included operative and oncologic parameters, length of stay (LOS), morbidity, and mortality. From November 2006 to August 2014, 41 patients (6 females) with a mean age of 65 years underwent RATE without surgical drainage of the pylorus. There were 14 patients in the BOTOX group and 27 patients in the noBOTOX group. Mean operative time was not different between the comparison groups. There was one conversion to open surgery in the BOTOX group. No pyloric dysfunction occurred in the BOTOX group postoperatively, and eight stenoses in the noBOTOX group (30%) required endoscopic therapy (P < .05). There were no differences in incidence of anastomotic strictures or anastomotic leaks. One patient in group noBOTOX required pyloroplasty 3 months after esophagectomy. There was one death in the noBOTOX group postoperatively (30-day mortality 2.4%). Mean LOS was 9.6 days, and BOTOX patients were discharged earlier (7.4 versus 10.7, P < .05). Intraoperative endoscopic injection of botulinum toxin into the pylorus during RATE is feasible, safe, and effective and can prevent the need for pyloromyotomy.

Botulinum Toxin A Upregulates Rac1, Cdc42, and RhoA Gene Expression in a Dose-Dependent Manner: In Vivo and in Vitro Study.

Angiogenesis is the development of new capillaries from existing blood vessels and is a prerequisite for the wound-healing process. Many lines of scientific evidences have shown that complicated roles of small guanosine triphosphatases (GTPases) (ras-related C3 botulinum toxin substrate 1 [Rac1], cell division control protein 42 [Cdc42], and ras homolog gene family, member A [RhoA]) in regulation of signal transduction pathways exist to transmit distinct cellular effects on the modulation of actin cytoskeleton remodeling such as cell cycle progression, cell survival, and cell motility. In addition, these small GTPases activate mitogen-activated protein kinase kinase kinases (MAP3Ks) leading to activated mitogen-activated protein kinase kinases (MAPKK), mitogen-activated protein kinase (MAPK), and various transcription factors such as vascular endothelial growth factor with involvement of MAPK signaling pathways.In this study, the authors hypothesized that botulinum toxin A increases angiogenesis via the expression of small GTPases in vivo and in vitro studies.In vivo experiment, 24 Sprague-Dawley rats were randomly divided into 2 groups: a control group and a botulinum toxin A group. Five days prior to superiorly based transverse rectus abdominis myocutaneous flap elevation, the botulinum toxin A (BoTA) group was pretreated with BoTA, while the control group was pretreated with normal saline. quantitative real-time polymerase chain reaction was performed to evaluate the expression of Rac1, RhoA, and Cdc42.The angiogenic effects of botulinum toxin A on human dermal fibroblasts were measured in vitro experiment. To understand the mechanism of botulinum toxin A on small GTPases production of fibroblasts, Rac1, Cdc42, and RhoA were measured using qRT-PCR.The relative messenger ribonucleic acid expression of Rac1, RhoA, and Cdc42 was significantly higher in the BoTA group than in the control group, in every zone and pedicle muscle, on postoperative days 1, 3, and 5. Levels of these molecules increased significantly in human dermal fibroblasts grown in the presence of BoTA compared with control group over 5 IU.Our in vivo and in vitro studies suggest that administration of BoTA upregulates the expression of RhoA, Rac1, and Cdc42 in a dose-dependent manner. MAPK signaling pathway might be involved in BoTA-induced angiogenesis mechanism. N/A.

Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model

Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the invivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. Ten 1-year-old female New Zealand White rabbits (average 5.7kg, range 4.8-6.6kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-β, IL-1 and IL-6 compared to the healthy controls. BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA.

Safety and Efficacy of Botulinum Toxin A in Children Undergoing Lower Limb Lengthening and Deformity Correction: Results of a Double-blind, Multicenter, Randomized Controlled Trial.

Lengthening of the lower limb is a complex procedure in which pain management and complications such as pin-site infections and muscle contractures impact the family and affect the child's quality of life. As a result, the paralytic and antinociceptive actions of neurotoxins may be indicated in managing these complications; however, few studies have explored ways to improve outcomes after lengthenings. The objective of this study was to evaluate the safety and efficacy of botulinum toxin A (BTX-A) in children undergoing lower limb lengthenings and deformity correction. Participants with a congenital or acquired deformity of the lower extremity requiring surgery to one limb were randomized to receiving either BTX-A as a single dose of 10 units per kilogram body weight, or an equivalent volume of saline solution. Pain, medication, quality of life, and physical function were assessed at different time-points. Adverse events were recorded in all participants. T test and χ tests were used to compare potential differences across both groups. Mean age of the 125 participants was 12.5 years (range, 5 to 21 y), and lengthenings averaged 4.2 cm. Maximum pain scores on day 1 postoperatively were lower in the BTX-A group (P=0.03) than in the placebo group, and remained significant favoring botox when stratifying by location of lengthening (femur vs. tibia). Clinical benefits for BTX-A were found for 3 quality of life domains at mid-distraction and end-distraction. When stratifying according to location of lengthening, there were significantly fewer pin-site infections in the tibia favoring botox (P=0.03). The amount of adverse events and bone healing indices were no different in both groups. The clinical differences in quality of life, the lower pain on the first postoperative day, and the lower number of pin-site infections in the tibia favoring BTX-A support its use as an adjunctive treatment to the lengthening process. The detailed analyses of pain patterns help inform families on the pain expectations during lower limb lengthenings. The amount of adverse events were no different in both groups, and bone healing rates were similar, indicating that the use of BTX-A in children undergoing limb lengthening and deformity correction is safe. Level I.

Safety of Botulinum Toxin Type A for Children With Nonambulatory Cerebral Palsy.

To determine safety of intramuscular botulinum toxin A (BoNT-A) injections to reduce spasticity and improve care and comfort of nonambulatory children with cerebral palsy (CP). Nonambulatory children with CP were randomly allocated to receive either BoNT-A (n = 23) or sham procedure (n = 18) in Cycle 1. In Cycle 2, the BoNT-A group received a second episode of BoNT-A (n = 20) and sham group received their first episode of BoNT-A (n = 17). A pediatric rehabilitation specialist masked to group allocation graded each adverse event (AE) according to system, severity (mild, moderate, serious, sentinel) and causality (unlikely/unrelated; possible; probable/definite). There was no difference for all moderate/serious AEs between the BoNT-A and sham/control groups in either Cycle 1 (incident rate ratio = 1.30, 95% confidence interval = 0.43-4.00; P = .64) or Cycle 2 (incident rate ratio = 0.72, 95% confidence interval = 0.30-1.75; P = .47). In Cycle 2, 1 serious, 3 moderate (single-episode group), and 24 mild (single-episode group n = 10; 2 episode group n = 14) AEs were probably/definitely related to BoNT-A. Children receiving BoNT-A were at no greater risk of moderate/serious AEs compared with a sham control procedure. There was no increased risk of moderate/serious AEs between one and two episodes of BoNT-A.

Effects of botulinum toxin A and/or bimanual task-oriented therapy on upper extremity activities in unilateral Cerebral Palsy: a clinical trial.

BackgroundThis study reports on the effects of botulinum toxin A (BoNT-A) injections in the upper extremity (UE) in children with unilateral Cerebral Palsy (uCP) combined with bimanual task-oriented therapy (BITT) or either treatment modality performed separately. Bimanual activities were measured with the Assisting Hand Assessment (AHA), the ABILHand-Kids questionnaire (AK), the Observational Skills Assessment Score (OSAS). Goal achievement was measured with Goal Attainment Scaling (GAS), using blind video assessment, and the Canadian Occupational Performance Measure (COPM).MethodsThirty-five children, mean age 7.14 years (SD 2.63), 11 Manual Ability Classification Score (MACS) I, 15 MACS II and 9 MACS III, participated. The trial started with four study groups: BoNT-A-only (n = 5), BITT-only (n = 11), BoNT-A + BITT (n = 13), and control (n = 6). Twenty-two children were randomised, 13 children received their parents’ preferred treatment: BoNT-A + BITT or BITT-only. Three comparisons were analysed: BITT (BoNT-A + BITT and BITT-only; n = 24) versus no BITT (BoNT-A-only and control; n = 11), BoNT-A (BoNT-A-only and BoNT-A + BITT; n = 18) versus no BoNT-A (BITT-only and control; n = 17), and the additional effect of BoNT-A (BoNT-A + BITT versus BITT-only). Follow-up time: 24 weeks.ResultsNo significant differences between the groups were found on the AHA. The amount of use of both hands on the OSAS was significantly better in the BoNT-A group in the beading and sandwich-making task. The BoNT-A group also showed significant improvement in the quality scores of the OSAS: the wrist position during grasping and holding, especially in the younger children. The BITT group improved significantly on the AK and significantly more on the performance and satisfaction scores of the COPM at 12 and 24 weeks regarding several goals. BoNT-A showed a significant negative effect at 12 and 24 weeks in the most important goal. BITT, more than BoNT-A + BITT, showed positive effects on the GAS score at 12 (significant), 18 and 24 weeks.ConclusionsBoNT-A has a positive effect on quality of movement and amount of use of the affected UE during the 3 months’ working time. BoNT-A has no additional effect on bimanual performance and goal achievement. BITT has a positive effect on goal achievement and bimanual performance, even up to 6 weeks after therapy had stopped.Trial registration: Current Controlled Trials ISRCTN69541857.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0404-3) contains supplementary material, which is available to authorized users.